Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Our previous work has shown that injection into mice of lipopolysaccharide (LPS) and the cytokines interleukin 1 (IL-1) and tumour necrosis factor (TNF) induces histidine decarboxylase (HDC), the enzyme forming histamine, in various tissues such as liver, lung, spleen and bone marrow, but not in the blood. The induction of HDC also occurs in nude mice and mast cell-deficient mice. On the other hand, haematopoietic cytokines such as IL-3, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) only induce HDC in the haematopoietic organs, i.e. bone marrow and spleen. In the present study, the effect of macrophage depletion on the induction of HDC was examined. 2. On day 1 after a single intravenous injection of a macrophage depletor (liposomes encapsulating dichloromethylene diphosphonate, which is toxic when ingested into macrophages), macrophages were almost completely depleted in the liver and reduced by about 50% in the spleen and bone marrow, but not significantly affected in the lung. On day 3, the degrees of the depletion were similar to those of day 1. In the spleen, macrophages were depleted in the red pulp, and there was a structural destruction. 3. In macrophage-depleted mice, the induction of HDC by LPS, IL-1 alpha or TNF-alpha was not impaired in the liver, and was potentiated in the lung and bone marrow. The induction of HDC was decreased only in the spleen at day 3. 4. HDC was not induced by LPS in the spleen of the adult rat, which is correspondingly inactive in haematopoiesis.5 These results indicate that the major cells in which HDC activity is induced in response to LPS, IL-1 and TNF are not circulating granulocytes, circulating monocytes, T cells derived from thymus, mast cells or phagocytic macrophages. Based on these results, we discuss the possibility that the major cells in which HDC was induced in non-haematopoietic and haematopoietic organs were endothelial cells and haematopoietic precursor cells respectively.
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PMID:Effects of macrophage depletion on the induction of histidine decarboxylase by lipopolysaccharide, interleukin 1 and tumour necrosis factor. 771 16

We recently showed that bone marrow-derived mast cells bore MHC class II molecules and could present antigens to specific T cell hybridomas. This article summarizes the effects of purified recombinant cytokines on the expression of MHC class II molecules by mast cells and on their antigen-presenting capacity. Since IL-3 is essential for mast cell growth, all the cytokines were analyzed in the presence of IL-3. IL-3 downregulated the production of Ia molecules, so that mast cells cultured in IL-3 alone had no antigen presenting ability. In contrast, IL-4 and IFN-gamma upregulated the production of MHC class II molecules, while GM-CSF had no effect. The antigen-presenting capacity of IL-4-treated mast cells was substantially enhanced by incubating these cells with GM-CSF for 2 days. GM-CSF enhanced antigen presentation only in combination with IL-4. The activation of mast cells was reversible and could not be repeated. Finally, incubation of IL-4- or IL-4/GM-CSF-treated mast cells with IFN-gamma led to almost complete inhibition of the antigen-presenting function. These findings provide new insights into the regulation of specific allergic responses.
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PMID:Presentation of soluble antigens by mast cells: upregulation by interleukin-4 and granulocyte/macrophage colony-stimulating factor and downregulation by interferon-gamma. 775 29

Mouse mast cells produce many kinds of cytokines in response to cross-linking of high affinity Fc epsilon receptor (Fc epsilon RI). Among these cytokines, granulocyte-macrophage CSF (GM-CSF) gene induction in mouse mast cells has been reported to be regulated at both the transcriptional level and the post-transcriptional level. We analyzed the mechanism of the transcriptional regulation of GM-CSF gene induction through Fc epsilon RI cross-linking stimulation in the mouse mast cell line MC/9. In MC/9, the GM-CSF gene was activated transcriptionally by Fc epsilon RI cross-linking stimulation. The 5' deletion analysis of GM-CSF gene promoter indicated that the 5' boundary of the responsive promoter region lay between positions -113 and -95. When the deletion was extended to positions -72 or -60, the stimulatory effect was significantly diminished. We then examined 3' deletion of pmGMCAT -113 from position -60. This analysis indicated that the 3' boundary lay between positions -84 and -72. No subfragments of the region spanning positions -113 to -72 could cover the full induction level. A site-directed mutagenesis experiment revealed that the sequence spanning positions -108 to -72 was needed for full activation. These data indicate that GM-CSF gene in mast cells is activated mainly through the sequence spanning positions -108 to -72.
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PMID:Cis-acting DNA elements of mouse granulocyte-macrophage colony-stimulating factor gene responsive to Fc epsilon receptor cross-linking stimulation in the mouse mast cell line MC/9. 781 76

The IL-3 receptor (IL-3R) is composed of alpha and beta subunits. Two homologous beta subunits of IL-3R are present in the mouse: AIC2A is the IL-3 specific beta subunit, and AIC2B is the common beta subunit shared by IL-3, IL-5 and granulocyte macrophage colony stimulating (GM-CSF) factor receptors. Both beta subunits form functionally indistinguishable high-affinity IL-3Rs with the same IL-3R specific alpha subunit (IL-3R alpha or SUT-1). Cell surface expression of the alpha and beta subunits of IL-3R was found to be diminished in an IL-3 non-responsive variant (MC/9.IL-4) derived from an IL-3-dependent mast cell line, MC/9. This IL-3R-defective phenotype was dominant based on cell fusion experiments. Moreover, regulatory mechanisms of the alpha and beta subunits are distinct since cell hybrids between MC/9.IL-4 and a CTLL-2 transfectant (CTLL/AS) expressing AIC2A and IL-3R alpha showed a significantly reduced expression of the AIC2A mRNA, while the IL-3R alpha expression was unchanged. Since transcription of both AIC2A and IL-3R alpha cDNAs in the CTLL/AS was driven by an artificial promoter, SR alpha, and nuclear run-off assays showed similar transcriptional rates of the AIC2A gene in both CTLL/AS and the cell hybrids between MC/9.IL-4 and CTLL/AS, the dominant suppression of the beta subunits is post-transcriptional and sequence-specific. A target sequence of the negative regulator must be present within 2756 bases of AIC2A mRNA, which is transcribed from the transfected cDNA in CTLL/AS cells. Similar dominant suppression of the beta subunit expression was also found in a B cell line WEHI231. As the negative regulator suppresses expression of the beta subunits of IL-3, IL-5 and GM-CSF receptors, it has the potential to eliminate all three high-affinity receptors simultaneously.
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PMID:Regulation of IL-3 receptor expression: evidence for a post-transcriptional mechanism that dominantly suppresses the expression of beta subunits. 782 43

While LCF is present in BAL early after antigen challenge, we know little about its other potential effects beyond CD4+ T cell, monocyte, and eosinophil chemotaxis and monocyte and CD4+ T cell activation. The work described here focuses on the hypothesis that the secreted protein products of T cells participate in the airway inflammatory process that underlies human asthma, and in particular that LCF could play an early role because of the unusual responsiveness of LCF-producing T to histamine. To date, most studies have addressed the measurement of cytokines derived from CD4+ T cells (e.g., IL-2, IL-3, IL-4, IL-5, and GM-CSF) in the airways of asthmatics, and attempted to correlate the presence of protein or mRNA with the complexion of the inflammatory infiltrate. These studies have been based upon the reports that there are increased numbers of CD4+ T cells in the airways of asthmatics, and that the presence of eosinophils might correlate with the secretion of TH2-type cytokines like IL-3, -4, and -5. Using this information as a background, our work has approached the problem in an entirely different way. We have focused our attention on the early events in antigen-induced asthma that are responsible for CD4+ cell accumulation in the lung, including CD4+ T cells, eosinophils, and monocytes. We have attempted to identify mechanisms by which mast cell mediators, in particular histamine, might play a role in the secretion of chemotactic lymphokines that are selective for CD4+ cells by using CD4 itself as a chemotactic factor receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokine binding to CD4+ inflammatory cells: implications for asthma. 795 94

To measure the effect of endogenous IL-3 (Multi-CSF) expression on hematopoietic cells in vivo, we have infected several kinds of hematopoietic cell populations with retroviral vectors carrying the IL-3 gene (M3MuV) in vitro and injected the virus-producing cells into mice to "target" the virus to sites of hematopoiesis. Mast cell lines (Elut cells) or multipotent cell lines (FDC-Pmix) were infected with MPSV-based replication defective retroviral vectors carrying either the neomycin resistance gene alone (M3neoV) or the neomycin gene plus the IL-3 gene (M3MuV). These cell lines produced infective retroviral particles consisting of the replication defective vectors and helper virus constitutively produced by the target cell populations. Irradiated and non-irradiated virus-producing Elut cells and the virus-producing FDC-Pmix cells were transplanted into syngeneic mice to "target" virus infection to the sites of hemopoiesis. Control mice injected with M3neoV-producing cells did not develop a disease up to 6 months following transplantation, whereas mice injected with M3MuV-producing cells developed a myeloproliferative disease within 3 months. Hematopoietic cell lines were rescued from diseased and control mice. In all cases these cell lines were of host origin. Cell lines derived from control mice were of basophil/mast cell morphology only, and required IL-3 for their continued proliferation (similar to cell lines derived from uninfected animals), whereas the cell lines generated from spleen and bone marrow cells of host mice with myeloproliferative disease carried the M3MuV vector, were G418 resistant and IL-3 independent. The biologic properties of M3MuV infected host derived cell lines varied considerably. Some were multipotential and could be induced to differentiate in response to stromal cells and serum factors, others were more restricted to the granulocyte/macrophage lineage but were also differentiation inducible, and some were blocked in differentiation at the myeloblast/promyelocyte stage. We conclude that the injected donor cells acted as "infectious centers" to facilitate the infection of host hematopoietic cells with the M3MuV vector. Our results indicate that the "targeted" in vivo infection of primitive hematopoietic cells with M3MuV can initiate the immortalization and leukaemogenesis of multipotential and lineage restricted progenitor cells.
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PMID:Targeted in vivo infection with a retroviral vector carrying the interleukin-3 (multi-CSF) gene leads to immortalization and leukemic transformation of primitive hematopoietic progenitor cells. 810 37

The supernatant (CM) of long-term bone marrow culture (LTBMC) contains colony promoting activity (CPA) which does not have granulocyte-macrophage (GM) colony-stimulating activity but which enhances GM-colony formation in the presence of CSF. CPA is different from IL-1, IL-3 and GM, G-, and M-CSF. Since CPA-containing LTBMC-CM always contains a substantial level of IL-6, CPA was thought to be similar to IL-6. In the present study, we found that LTBMC with a particular batch of horse serum produced IL-6 without a corresponding production of CPA. Addition of IL-6 to GM-colony assay system in the presence of GM-CSF did not enhance the colony formation. LTBMC-CM did not stimulate proliferation nor differentiation of mast cell progenitors. Anti-IL-6 antibodies suppressed IL-6 activity, but not CPA. These results indicate that CPA is a novel factor distinct from IL-1, IL-3, G-, M-, GM-CSF, IL-6 and SCF (c-kit ligand).
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PMID:Colony promoting activity (CPA) is a novel factor distinct from IL-6. 821 51

Interleukin-10 (IL-10) is a novel cytokine that is produced by T cells, macrophages, B cells and keratinocytes. It has been shown to inhibit cytokine production and proliferation by T cells when macrophages are used as accessory or antigen presenting cells. Monokine production by macrophages is effectively downregulated by IL-10 and it can be used as a growth factor by CD4, CD8 and gamma/delta positive T cells as well as mast cells and B cells. It is because of these pleiotropic immunoregulatory effects that the detection of IL-10 in the supernatants of T cells, B cells, macrophages and other cells is important for many scientific questions. Here we describe a simple and sensitive bioassay specific for human IL-10 using the IL-10 dependent growth of the mouse mast cell line D36. Our data show that this assay is not crossreactive with hIL-1 beta, hIL-2, hIL-3, hIL-4, hIL-5, hIL-6, hIL-9, hIL-12, hGM-CSF and hTNF-alpha and that it can be completely blocked by an antibody against human IL-10. The hIL-10 induced growth of the D36 cell line is dependent on the presence of mIL-4. Human IL-10 can be measured in a concentration range from approximately 10 U/ml to 0.05 U/ml. This assay is only of limited use for the measurement of IL-10 in human blood samples since it is inhibited by the presence of human serum.
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PMID:A sensitive and specific bioassay for the detection of human interleukin-10. 828 94

To establish the method for generating a large number of mature human mast cells, we cultured cord blood mononuclear cells (CBMC) in several conditions in the presence of Steel factor (SF). Among several cytokines tested, IL-6 enhanced SF-dependent mast cell growth from purified CD34+ cells for more than 8 wk in culture. When CBMC were cultured instead of CD34+ cells, IL-6 enhanced the mast cell development in the presence but not in the absence of PGE2. PGE2 enhanced the SF- and IL-6-dependent development of mast cells from CBMC probably by blocking granulocyte-macrophage CSF (GM-CSF) secretion from accessory cells, because 1) PGE2, or anti-GM-CSF enhanced the mast cell development induced by SF and IL-6 from CBMC, but not from CD34+ cells; 2) GM-CSF inhibited the enhancing effect of IL-6 on the mast cell development from CD34+ cells; and 3) PGE2 inhibited GM-CSF secretion from CBMC. The mast cells cultured in the presence of SF, IL-6, and PGE2 for >10 wk were 99% pure, and seemed to be functionally mature, because 1) they contained 5.62 micrograms of histamine and 3.46 micrograms of tryptase per 10(6) cells; and 2) when sensitized with human IgE and then challenged with anti-human IgE, the cells released a variety of mediators such as histamine, and an increase in intracellular Ca2+ was found in advance of the activation of membrane movement by using a confocal laser-scanning microscope. Electron-microscopic analysis revealed that some of the cultured mast cells are morphologically mature since they filled with scroll granules and contained crystal granules.
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PMID:Selective growth of human mast cells induced by Steel factor, IL-6, and prostaglandin E2 from cord blood mononuclear cells. 868 36

The basic helix-loop-helix (bHLH) transcription factors form heterodimers and control steps in cellular differentiation. We have studied four bHLH transcription factors, SCL, lyl-1, E12/E47, and ld-1, in individual lineage-defined progenitors and hematopoietic growth factor-dependent cell lines, evaluating mRNA expression and the effects of growth factors and cell cycle phase on this expression. Single lineage-defined progenitors selected from early murine colony starts and grown under permissive conditions were analyzed by RT-PCR. SCL and E12/E47 were expressed in the vast majority of tri-, bi-, and unilineage progenitors of erythroid, macrophage, megakaryocyte, and neutrophil lineages. Expression for E12/E47 was not seen in unilineage megakaryocyte and erythroid or bilineage neutrophil/mast cell progenitors. Lyl-1 showed a more restricted pattern of expression, although expression was seen in some bi- and unilineage progenitors. No expression was detected in erythroid, erythroid-megakaryocyte-macrophage, macrophage-neutrophil, macrophage, or megakaryocytic progenitors. Id-1, an inhibitory bHLH transcription factor, was also widely expressed in all bi- and unilineage progenitors; only the trilineage erythroid-megakaryocyte-macrophage progenitors failed to show expression. Expression of these factors within a progenitor class was generally heterogeneous, with some progenitors showing expression and some not. This was seen even when two sister cells from the same colony start were analyzed. Id-1, but not E12/E47, mRNA was increased in FDC-P1 and MO7E hematopoietic cell lines after exposure to IL-3 or GM-CSF. Id-1, E12, and lyl-1 showed marked variation at different points in cell cycle in isoleucine-synchronized FDC-P1 cells. These results suggest that SCL, lyl-1, E12/E47, and Id-1 are important in hematopoietic progenitor cell regulation, and that their expression in hematopoietic cells varies in response to cytokines and/or during transit through cell cycle.
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PMID:Expression of basic helix-loop-helix transcription factors in explant hematopoietic progenitors. 876 52


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